Hepatic functions elimination

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Renal and/or hepatic function should be considered in every patient prior to initiation of antimicrobial therapy. In general, most antimicrobials undergo renal elimination and... 

Thus, in critically ill patients where catheters are conventionally inserted for diagnostic or therapeutic interventions, incorporation of the appropriate fiber optics to commercial catheters would enable the monitoring of hepatic function continuously and simultaneously with other medical interventions. Previous studies by the absorption method also found a close correlation between invasive and noninvasive ICG plasma elimination kinetics [157,160]. 

Priapism Priapism has been reported from postmarketing surveillance of tinzaparin as a rare occurrence. In some cases, surgical intervention was required. Renal/Hepatic function impairment Delayed elimination of LMWHs may occur with severe liver or kidney insufficiency. Use with caution. 

Renal/Hepatic function impairment Hepatic impairment may result in inadequate release of glucose in response to hypoglycemia. Renal impairment may cause decreased elimination of sulfonylureas leading to accumulation producing hypoglycemia. 

Hepatic function impairment Subjects with hepatic disease had a 28.3% decrease in plasma clearance of nalmefene compared with controls (0.56 vs 0.78 L/h/kg, respectively). Elimination half-life increased from 10.2 to 11.9 hours in the hepatically impaired. No dosage adjustment is recommended because nalmefene will be administered as an acute course of therapy. 

Hepatic function impairment Propafenone is highly metabolized by the liver administer cautiously to patients with impaired hepatic function. The clearance of propafenone is reduced and the elimination half-life increased in patients with significant hepatic dysfunction. The dose of propafenone should be approximately 20% to 30% of the dose given to patients with normal hepatic function. 

Hepatic function impairment Since mexiletine is metabolized in the liver, and hepatic impairment prolongs the elimination half-life, carefully monitor patients with liver disease. Observe caution in patients with hepatic dysfunction secondary to CHF. Abnormal liver function tests have been reported, some in the first few weeks of therapy with mexiletine. Most have occurred along with CHF or ischemia their relationship to mexiletine has not been established. 

Hepatic function impairment Because flecainide elimination from plasma can be markedly slower in patients with significant hepatic impairment, do not use in such patients unless the potential benefits outweigh the risks. If used, make dosage increases very cautiously when plasma levels have plateaued (after more than 4 days). 

Hepatic function impairment Because iloprost elimination is reduced in patients with impaired liver function, exercise caution during iloprost therapy in patients with at least Child-Pugh class B hepatic impairment. 

Hepatic function impairment The elimination half-life of tolterodine was longer in cirrhotic patients (mean, 8.7 hours) than in healthy, young, and elderly volunteers (mean, 2 to 4 hours). The clearance of oral tolterodine was substantially lower in cirrhotic patients (approximately 1.1 L/h/kg) than in the healthy volunteers (approximately 5.7 L/h/kg). 

Special risk Caution is advised when using lamotrigine in patients with diseases or conditions that could affect metabolism or elimination of the drug, such as renal or hepatic function impairment (see Warnings) or cardiac function impairment. Caution is advised when using lamotrigine in patients with diseases or conditions that could affect metabolism or elimination of the drug, such as renal, hepatic, or cardiac functional impairment. 

Hepatic function impairment There are no data in patients with severe cirrhosis. Dosage adjustment is recommended in patients with mild-to-moderate cirrhosis. Eideriy Norfloxacin is eliminated more slowly because of decreased renal function. The apparent half-life of ofloxacin is 6 to 8 hours, compared to approximately 5 hours in younger adults. Lomefloxacin plasma clearance was reduced by 25% and the AUC was increased by approximately 33% in the elderly. 

Renai/Hepatic function impairment The safety and pharmacokinetics of rimantadine in renal and hepatic insufficiency only have been evaluated after single dose administration. In a single dose study of patients with anuric renal failure, the apparent clearance was approximately 40% lower and the elimination half-life was 1.6-fold greater than that in healthy controls. In a study of 14 people with chronic liver disease (mostly stabilized cirrhotics), no alterations in the pharmacokinetics were observed after a single dose of rimantadine. However, the apparent clearance of rimantadine following a single dose to 10 patients with severe liver dysfunction was 50% lower than that reported for healthy subjects. Because of the potential for accumulation of rimantadine and its metabolites in plasma, exercise caution when patients with renal or hepatic insufficiency are treated with rimantadine. 

Hepatic function impairment- Because zidovudine is primarily eliminated by hepatic metabolism, a reduction in the daily dose may be necessary in these patients. Frequent monitoring for hematologic toxicities is advised. 

Renal/Hepatic function impairment Zidovudine is eliminated from the body primarily by renal excretion following metabolism in the liver (glucuronidation). In patients with severely impaired renal function (Ccr less than 15 mL/min), dosage reduction is recommended. Although very little data are available, patients with severely impaired hepatic function may be at greater risk of toxicity. 

Because insomnia is often transient and intermittent, the prolonged administration of estazolam is generally neither necessary nor recommended. Caution should be exercised in prescribing this hypnotic for elderly or debilitated patients, as well as for those with impaired renal or hepatic function, because of increased sensitivity or reduced capacity to metabolize and eliminate the drug. The recommended initial dose is 1 mg, but some may need a 2 mg dose. For the elderly, a 0.5 or 1 mg dose is appropriate. 

It is also important to remember that these agents are primarily metabolized by the liver, and because various medical disorders can compromise hepatic function (e.g., congestion secondary to heart failure, metastases, or cirrhotic states), the elimination half-lives of these drugs may be significantly prolonged. This may lead to excessive accumulation over several days to weeks of treatment, ultimately culminating in further deterioration. Thus, the judicious use of as-needed or short-term drug use is ideal. 

Hence, a study in individuals with impaired hepatic function may also be recommended if the liver is not the maj or organ for elimination, or if the drug has a narrow therapeutic window, or in case the metabolism is unknown and other information is lacking. 

Measurements such as creatinine clearance have been used successfully to adjust dosing regimens for drugs eliminated primarily by the kidneys. Measures of hepatic function have been sought using endogenous... 

In summary, a pharmacokinetic study in individuals with impaired hepatic function is recommended if the extent of hepatic metabolism is unknown, the hepatic metabolism/excretion accounts for > 20 % of the elimination of parent drag or metabolite(s), and for drugs with a narrow therapeutic window. The primary goal of such a study is to determine if the pharmacokinetic is altered to an extent that the dose and/or dosing regimen of a drug should be adjusted from that established in the confirmatory safety and efficacy trials. 

In contrast to renal impairment, no obvious marker exists for characterizing hepatic function with respect to predictions of drug elimination capacity. Therefore, dose recommendations may not be as accurate for hepatic impairment as for renal impairment. 

In elderly people there is much slower recovery from nondepolarizing relaxants (about 60% in patients over 75 years of age given pancuronium), associated with a decreased rate of elimination (probably through reduced glomerular clearance and, to a lesser extent, reduced hepatic blood flow). The potency of relaxants is not altered. While the initial dose required to produce full relaxation is the same as in young adults, smaller maintenance doses are required at much longer intervals (95,96). The duration of action of atracurium is not increased, since termination of its action does not depend on renal or hepatic function. 

Because of the importance of hepatic metabolism in SN-38 elimination by glucuronidation, the biliary clearance of irinotecan and its metabolites is delayed in patients with impaired hepatic function (55-57), and there is a negative correlation between serum bilirubin concentrations and the total body clearance of irinotecan. In a patient with moderately impaired liver function, it was necessary to reduce the dose to 100 mg/m instead of 350 mg/m intravenously thrice-weekly, in order to achieve half-lives and C ax values of irinotecan and SN-38 comparable to those observed in patients with normal liver function (55). However, the corresponding AUCs were still significantly increased, resulting in more severe leukopenia and delayed diarrhea. The authors concluded that to improve tolerance, exposure to the drug in a patient of this kind should not exceed 30 mg/m intravenously. 

The onset of neuromuscular blockade typically occurs in 3-5 min of i.v. administration and lasts for 20-35 min. Higher doses will result in a longer duration of blockade. Pancuronium is eliminated primarily in bile and vecuronium undergoes hepatic and renal excretion. The recovery from blockade produced by atracurium is a result of metabolism by non-specific plasma esterases (hydrolysis) and spontaneous Hoffman degradation (spontaneous at body temperature and physiological pH), which is independent of renal or hepatic function and, therefore, unaffected by renal or hepatic disease (Plumb 1995). Atracurium does not accumulate. 

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